J Bone Metab.  2014 Nov;21(4):249-255. 10.11005/jbm.2014.21.4.249.

Effect of Zoledronate on the Expression of Vascular Endothelial Growth Factor-A by Articular Chondrocytes and Synovial Cells: An in Vitro Study

• Yi JW
• Lee WS
• Kim SB
• Heo YM
• Chae DS

• KMID: 2170052
• DOI: http://doi.org/10.11005/jbm.2014.21.4.249

Abstract

BACKGROUND
The aim of this in vitro study was to determine the effect of zoledronate, which is frequently used to treat osteoporosis, on osteoarthritis by analyzing zoledronate-induced expression of vascular endothelial growth factor-A (VEGF-A) in chondrocytes and synovial cells.
METHODS
After chondrocytes and synovial cells were separated and cultured, zoledronate was added, and VEGF-A and pigment epithelium-derived factor (PEDF) expression were quantified by real-time polymerase chain reaction and Western blotting.
RESULTS
There was no significant difference in the expression of VEGF-A mRNA in chondrocytes between the zoledronate group and the control group on the 8th day of culture. The expression of both VEGF-A and PEDF mRNA in synovial cells was significantly decreased in the zoledronate group (P<0.05).
CONCLUSIONS
Zoledronate decreases the expression of VEGF-A in synovial cells and may affect the development and progression of osteoarthritis.

Keyword

Chondrocytes; Osteoarthritis; Synovial cells; Vascular endothelial growth factor-A; Zoledronate

MeSH Terms

Blotting, Western
Chondrocytes*
Osteoarthritis
Osteoporosis
Real-Time Polymerase Chain Reaction
RNA, Messenger
Vascular Endothelial Growth Factor A*
RNA, Messenger
Vascular Endothelial Growth Factor A

Figure

• 

  Fig. 1 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results after culture of chondrocytes in scaffolds for 3, 5, and 8 days. Significant differences are found in the 10-5 mol/L and 10-4 mol/L groups of zoledronate (P<0.001).

• 

  Fig. 2 Proliferation of chondrocytes. Cell number increased in cells treated with 10-7 mol/L zoledronate relative to the control group by day 3, but this difference was not significant for each time point (P>0.05).

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  Fig. 3 Proliferation of synovial cells. Cell number decreased in cells treated with 10-7 mol/L zoledronate relative to the control group by day 8, but this difference was not significant for each time point (P>0.05).

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  Fig. 4 Expression of vascular endothelial growth factor-A (VEGF-A) mRNA in zoledronate-treated chondrocytes was lower than in the control group at day 8, but this difference was not significant (P=0.155). ZA, zoledronate.

• 

  Fig. 5 Expression of pigment epithelium-derived factor (PEDF) mRNA in zoledronate-treated chondrocytes was lower than in the control group at day 8, but this difference was not significant (P=0.631). ZA, zoledronate.

• 

  Fig. 6 Expression of vascular endothelial growth factor-A (VEGF-A) mRNA in zoledronate-treated synovial cells was significantly lower than in the control group at day 8 (*P=0.022). ZA, zoledronate.

• 

  Fig. 7 Expression of pigment epithelium-derived factor (PEDF) mRNA in zoledronate-treated synovial cells was significantly lower than in the control group at day 8 (*P=0.041). ZA, zoledronate.

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  Fig. 8 Western blot analysis for vascular endothelial growth factor (VEGF) & pigment epithelium-derived factor (PEDF) in chondrocytes and synovial cells with or without zoledronate revealed no significant difference in chondrocytes, but a significant difference in synovial cells (P=0.039, P=0.020). VEGF, vascular endothelial growth factor; PEDF, pigment epithelium-derived factor; ZA, zoledronate.

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